Gaetano Nucifora

Relative Merits of Left Ventricular Dyssynchrony, Left Ventricular Lead Position, and Myocardial Scar to Predict Long-Term Survival of Ischemic Heart Failure Patients Undergoing Cardiac Resynchronization Therapy

Background— The relative merits of left ventricular (LV) dyssynchrony, LV lead position, and myocardial scar to predict long-term outcome after cardiac resynchronization therapy remain unknown and were evaluated in the present study. Methods and Results— In 397 ischemic heart failure patients, 2-dimensional speckle tracking imaging was performed, with comprehensive assessment of LV radial dyssynchrony, identification of the segment with latest mechanical activation, and detection of myocardial scar in the segment where the LV lead was positioned. For LV dyssynchrony, a cutoff value of 130 milliseconds was used. Segments with <16.5% radial strain in the region of the LV pacing lead were considered to have extensive myocardial scar (>50% transmurality, validated in a subgroup with contrast-enhanced magnetic resonance imaging). The LV lead position was derived from chest x-ray. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Mean baseline LV radial dyssynchrony was 133±98 milliseconds. In 271 patients (68%), the LV lead was placed at the latest activated segment (concordant LV lead position), and the mean value of peak radial strain at the targeted segment was 18.9±12.6%. Larger LV radial dyssynchrony at baseline was an independent predictor of superior long-term survival (hazard ratio, 0.995; P=0.001), whereas a discordant LV lead position (hazard ratio, 2.086; P=0.001) and myocardial scar in the segment targeted by the LV lead (hazard ratio, 2.913; P<0.001) were independent predictors of worse outcome. Addition of these 3 parameters yielded incremental prognostic value over the combination of clinical parameters. Conclusions— Baseline LV radial dyssynchrony, discordant LV lead position, and myocardial scar in the region of the LV pacing lead were independent determinants of long-term prognosis in ischemic heart failure patients treated with cardiac resynchronization therapy. Larger baseline LV dyssynchrony predicted superior long-term survival, whereas discordant LV lead position and myocardial scar predicted worse outcome.

Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus

Regional left ventricular (LV) myocardial functional changes in early diabetic cardiomyopathy have not been well documented. LV multidirectional strain and strain rate analyses by 2-dimensional speckle tracking were used to detect subtle myocardial dysfunction in 47 asymptomatic, male patients (age 57 +/- 6 years) with type 2 diabetes mellitus. The results were compared to those from 53 male controls matched by age, body mass index, and body surface area. No differences were found in the LV end-diastolic volume index (40.7 +/- 8.9 vs 44.1 +/- 7.8 ml/m(2), p = NS), end-systolic volume index (16.0 +/- 4.8 vs 17.8 +/- 4.3 ml/m(2), p = NS), ejection fraction (61.0 +/- 5.5% vs 59.8 +/- 5.3%, p = NS). The transmitral E/A (0.95 +/- 0.21 vs 1.12 +/- 0.32, p = 0.007) and pulmonary S/D (1.45 +/- 0.28 vs 1.25 +/- 0.27, p = 0.001) ratios were more impaired in the patients with diabetes mellitus. Importantly, the diabetic patients had impaired longitudinal, but preserved circumferential and radial systolic and diastolic, function. Diabetes mellitus was an independent predictor for longitudinal strain, systolic strain rate and early diastolic strain rate on multiple linear regression analysis (all p <0.001). In conclusion, the LV longitudinal systolic and diastolic function were impaired, but the circumferential and radial functions were preserved in patients with uncomplicated type 2 diabetes mellitus.

Relation of Epicardial Adipose Tissue to Coronary Atherosclerosis

Adipose tissue surrounding the coronary arteries has been suggested to induce development of atherosclerosis. We explored the relation between epicardial adipose tissue (EAT) volume and coronary atherosclerosis using multislice computed tomography. The study population consisted of 190 patients who had undergone multislice computed tomographic coronary angiography. Coronary artery calcium score was assessed. In addition, patients were classified as having (1) no atherosclerosis, (2) nonobstructive atherosclerosis (luminal narrowing <50%), (3) obstructive atherosclerosis (luminal narrowing >or=50%) in a single vessel, or (4) obstructive atherosclerosis in the left main coronary artery and/or multiple vessels. Cross-sectional tomographic cardiac slices (3.00-mm thickness, range 35 to 40 slices per heart) were traced semiautomatically from the border of EAT below the apex to a point at the center of the left atrium. Tissue with values from -250 to -30 HU was assigned as EAT. EAT volume within the traced area was then automatically quantified. Mean EAT volume was 84 +/- 41 ml. Patients with a coronary artery calcium score >10 had significantly larger average EAT volume (100 +/- 40 ml) compared with patients with calcium scores <or=10 (59 +/- 27 ml, p <0.001). Sensitivity and specificity for prediction of a calcium score >10 were 77% and 70% with a cut-off EAT value of 73 ml. In patients with normal coronaries mean EAT volume (63 +/- 31 ml) was significantly smaller than in patients with atherosclerosis (99 +/- 40 ml, p <0.001). Using a cut-off EAT volume of 75 ml, the sensitivity and specificity for presence of atherosclerosis were 72% and 70%. Interestingly, quantity of EAT did not significantly increase with increasing extent or severity of atherosclerosis. After adjustments for risk factors EAT volume remained a significant predictor of coronary atherosclerosis (p = 0.001). In conclusion, a significant relation was shown between EAT volume and presence of coronary atherosclerosis. Quantification of EAT may be useful to identify patients at risk for coronary artery disease.

Alterations in multidirectional myocardial functions in patients with aortic stenosis and preserved ejection fraction: a two-dimensional speckle tracking analysis

AIMSnTo identify changes in multidirectional strain and strain rate (SR) in patients with aortic stenosis (AS).nnnMETHODS AND RESULTSnA total of 420 patients (age 66.1 ± 14.5 years, 60.7% men) with aortic sclerosis, mild, moderate, and severe AS with preserved left ventricular (LV) ejection fraction [(EF), ≥50%] were included. Multidirectional strain and SR imaging were performed by two-dimensional speckle tracking. Patients were more likely to be older (P < 0.001) and at a worse New York Heart Association functional class (P < 0.001) with increasing AS severity. There was a progressive stepwise impairment in longitudinal, circumferential, and radial strain and SR with increasing AS severity (all P < 0.001). The myocardial dysfunction appeared to start in the subendocardium with mild AS, to mid-wall dysfunction with moderate AS, and eventually transmural dysfunction with severe AS. Aortic valve area, as a measure of AS severity, was an independent determinant of multidirectional strain and SR on multiple linear regressions.nnnCONCLUSIONSnPatients with AS have evidence of subclinical myocardial dysfunction early in the disease process despite normal LVEF. The myocardial dysfunction appeared to start in the subendocardium and progressed to transmural dysfunction with increasing AS severity. Symptomatic moderate and severe AS patients had more impaired multidirectional myocardial functions compared with asymptomatic patients.

Quantification of Functional Mitral Regurgitation by Real-Time 3D Echocardiography: Comparison With 3D Velocity-Encoded Cardiac Magnetic Resonance

OBJECTIVESnThe aim of this study was to evaluate feasibility and accuracy of real-time 3-dimensional (3D) echocardiography for quantification of mitral regurgitation (MR), in a head-to-head comparison with velocity-encoded cardiac magnetic resonance (VE-CMR).nnnBACKGROUNDnAccurate grading of MR severity is crucial for appropriate patient management but remains challenging. VE-CMR with 3D three-directional acquisition has been recently proposed as the reference method.nnnMETHODSnA total of 64 patients with functional MR were included. A VE-CMR acquisition was applied to quantify mitral regurgitant volume (Rvol). Color Doppler 3D echocardiography was applied for direct measurement, in en face view, of mitral effective regurgitant orifice area (EROA); Rvol was subsequently calculated as EROA multiplied by the velocity-time integral of the regurgitant jet on the continuous-wave Doppler. To assess the relative potential error of the conventional approach, color Doppler 2-dimensional (2D) echocardiography was performed: vena contracta width was measured in the 4-chamber view and EROA calculated as circular (EROA-4CH); EROA was also calculated as elliptical (EROA-elliptical), measuring vena contracta also in the 2-chamber view. From these 2D measurements of EROA, the Rvols were also calculated.nnnRESULTSnThe EROA measured by 3D echocardiography was significantly higher than EROA-4CH (p < 0.001) and EROA-elliptical (p < 0.001), with a significant bias between these measurements (0.10 cm(2) and 0.06 cm(2), respectively). Rvol measured by 3D echocardiography showed excellent correlation with Rvol measured by CMR (r = 0.94), without a significant difference between these techniques (mean difference = -0.08 ml/beat). Conversely, 2D echocardiographic approach from the 4-chamber view significantly underestimated Rvol (p = 0.006) as compared with CMR (mean difference = 2.9 ml/beat). The 2D elliptical approach demonstrated a better agreement with CMR (mean difference = -1.6 ml/beat, p = 0.04).nnnCONCLUSIONSnQuantification of EROA and Rvol of functional MR with 3D echocardiography is feasible and accurate as compared with VE-CMR; the currently recommended 2D echocardiographic approach significantly underestimates both EROA and Rvol.

Incremental value of 2-dimensional speckle tracking strain imaging to wall motion analysis for detection of coronary artery disease in patients undergoing dobutamine stress echocardiography

BACKGROUNDnInterpretation of dobutamine stress echocardiogram (DSE) is often subjective and requires expert training. The purposes of this study was to determine optimal cutoff values for longitudinal, circumferential, and radial strains at peak DSE for detection of significant stenoses on coronary angiography and to investigate incremental value of combining strain measurements to wall motion analysis.nnnMETHODSnIn this multicenter study, 102 patients underwent concomitant DSE and coronary angiography. Optimal cutoff values for mean global longitudinal (-20%), global circumferential (-26%), and mean radial (50%) strains at peak stress for detection of significant stenoses on coronary angiography were determined in a derivation group (n = 62) and tested in a prospectively recruited validation group (n = 40).nnnRESULTSnRespective sensitivities for longitudinal, circumferential, radial strains, and expert wall motion score index (WMSI) were 84.2%, 73.9%, 78.3%, and 76%; respective specificities were 87.5%, 78.6%, 57.1%, and 92.9%; and respective accuracies were 85.2%, 75.7%, 70.3%, and 82.1%. Longitudinal strain analysis had comparable accuracy to WMSI (P = .70). However, combination longitudinal strain and WMSI had the highest sensitivity, specificity, and accuracy (100%, 87.5%, and 96.3% respectively), and its diagnostic accuracy was incremental to either longitudinal strain (P = .034) or WMSI alone (P = .008).nnnCONCLUSIONnLongitudinal strain analysis had higher diagnostic accuracy than circumferential and radial strains and was comparable to WMSI for detection of significant coronary artery disease. However, combination longitudinal strain and WMSI resulted in significant incremental increase in diagnostic accuracy.

Effects of Cardiac Resynchronization Therapy on Left Ventricular Twist

OBJECTIVESnThis study explored the effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) twist, particularly in relation to LV lead position.nnnBACKGROUNDnLV twist is emerging as a comprehensive index of LV function.nnnMETHODSnEighty heart failure patients were included. Two-dimensional echocardiography was performed at baseline, immediately after CRT, and at 6-month follow-up. Speckle-tracking analysis was applied to assess LV twist. The LV lead was placed preferably in a (postero)lateral vein, and at fluoroscopy, the position was classified as basal, midventricular, or apical. Response to CRT was defined as reduction of LV end-systolic volume>or=15% at 6-month follow-up. A control group comprised 30 normal subjects.nnnRESULTSnPeak LV twist in heart failure patients was 4.8+/-2.6 degrees compared with 15.0+/-3.6 degrees in the control subjects (p<0.001). At 6-month follow-up, peak LV twist significantly improved only in responders (56%), from 4.3+/-2.4 degrees to 8.5+/-3.2 degrees (p<0.001). The strongest predictor of response to CRT was the improvement of peak LV twist immediately after CRT (odds ratio: 1.899, 95% confidence interval: 1.334 to 2.703, p<0.001). Furthermore, LV twist significantly improved in patients with an apical (from 4.3+/-3.1 degrees to 8.6+/-3.0 degrees, p=0.001) and midventricular (from 4.8+/-2.2 degrees to 6.4+/-3.9 degrees, p=0.038) but not with a basal (5.0+/-3.3 degrees vs. 4.1+/-3.2 degrees, p=0.28) LV lead position. Similarly, LV ejection fraction significantly increased in patients with an apical (from 26+/-7% to 37+/-7%, p<0.001) and midventricular (from 26+/-6% to 33+/-8%, p<0.001) but not with a basal (26+/-5% vs. 28+/-8%, p=0.30) LV lead position.nnnCONCLUSIONSnAn immediate improvement of LV twist after CRT predicts LV reverse remodeling at 6-month follow-up.

Lack of improvement of clinical outcomes by a low-cost, hospital-based heart failure management programme.

Objective Heart failure (HF) is a major health problem resulting in a high financial burden for the healthcare system. Many previous HF management programmes reduced adverse clinical outcomes and costs, but they usually involved several professional figures as well as huge investments, requiring resources and budgets not often available in our healthcare system. We evaluated the effects of our HF management programme, which included patient education and regular outpatient contact with the HF team, on re-hospitalisation and death, optimising the few resources already available at our hospital. Methods Two hundred consecutive patients admitted to the internal medicine department with a diagnosis of HF were randomised to the intervention group (nurse-led education programme, facilitated telephone communication and follow-up visits with an internist at 15 days, 1 and 6 months) or to the usual care group (follow-up by their primary care physician). The primary endpoints were all-cause readmissions and all-cause deaths during the 6-month post-discharge period. Results There were 81 all-cause hospital readmissions in the intervention group and 82 in the control group (P = NS). Fourteen patients (14%) in the intervention group and eight patients (8%) in the control group died during the study period (P = NS). Unplanned outpatient visits were less frequent in the intervention group than in the control group (39 [28%] versus 99 [72%], P < 0.001). Conclusions The present low-cost HF management programme reduced unplanned outpatient visits but proved ineffective in reducing subsequent readmissions and in improving clinical status. More intense follow-up monitoring and more resources are needed to achieve better results.

Incremental value of subclinical left ventricular systolic dysfunction for the identification of patients with obstructive coronary artery disease.

BACKGROUNDnLeft ventricular (LV) diastolic dysfunction and subclinical systolic dysfunction may be markers of coronary artery disease (CAD). However, whether these markers are useful for prediction of obstructive CAD is unknown.nnnMETHODSnA total of 182 consecutive outpatients (54 +/- 10 years, 59% males) without known CAD and overt LV systolic dysfunction underwent 64-slice multislice computed tomography (MSCT) coronary angiography and echocardiography. The MSCT angiograms showing atherosclerosis were classified as showing obstructive (> or =50% luminal narrowing) CAD or not. Conventional echocardiographic parameters of LV systolic and diastolic function were obtained; in addition, (1) global longitudinal strain (GLS) and strain rate (indices of systolic function) and (2) global strain rate during the isovolumic relaxation period and during early diastolic filling (indices of diastolic function) were assessed using speckle-tracking echocardiography. In addition, the pretest likelihood of obstructive CAD was assessed using the Duke Clinical Score.nnnRESULTSnBased on MSCT, 32% of patients were classified as having no CAD, whereas 33% showed nonobstructive CAD and the remaining 35% had obstructive CAD. Multivariate analysis of clinical and echocardiographic characteristics showed that only high pretest likelihood of CAD (odds ratio [OR] 3.21, 95% 1.02-10.09, P = .046), diastolic dysfunction (OR 3.72, 95% CI 1.44-9.57, P = .006), and GLS (OR 1.97, 95% CI 1.43-2.71, P < .001) were associated with obstructive CAD. A value of GLS > or =-17.4 yielded high sensitivity and specificity in identifying patients with obstructive CAD (83% and 77%, respectively), providing a significant incremental value over pretest likelihood of CAD and diastolic dysfunction.nnnCONCLUSIONSnThe GLS impairment aids detection of patients without overt LV systolic dysfunction having obstructive CAD.

Plaque type and composition as evaluated non-invasively by MSCT angiography and invasively by VH IVUS in relation to the degree of stenosis

Background: Imaging of coronary plaques has traditionally focused on evaluating degree of stenosis, as the risk for adverse cardiac events increases with stenosis severity. However, the relation between plaque composition and severity of stenosis remains largely unknown. Objective: To assess plaque composition (non-invasively by multislice computed tomography (MSCT) angiography and invasively by virtual histology intravascular ultrasound (VH IVUS)) in relation to degree of stenosis. Methods: 78 patients underwent MSCT (identifying three plaque types; non-calcified, calcified, mixed) followed by invasive coronary angiography and VH IVUS. VH IVUS evaluated plaque burden, minimal lumen area and plaque composition (fibrotic, fibro-fatty, necrotic core, dense calcium) and plaques were classified as fibrocalcific, fibroatheroma, thin-capped fibroatheroma (TCFA), pathological intimal thickening. For each plaque, percentage stenosis was evaluated by quantitative coronary angiography. Significant stenosis was defined >50% stenosis. Results: Overall, 43 plaques (19%) corresponded to significant stenosis. Of the 227 plaques analysed, 70 were non-calcified plaques (31%), 96 mixed (42%) and 61 calcified (27%) on MSCT. Plaque types on MSCT were equally distributed among significant and non-significant stenoses. VH IVUS identified that plaques with significant stenosis had higher plaque burden (67% (11%) vs 53% (12%), p<0.05) and smaller minimal lumen area (4.6 (3.8–6.8) mm2 vs 7.3 (5.4–10.5) mm2, p<0.05). Interestingly, no differences were observed in percentage fibrotic, fibro-fatty, necrotic core and dense calcium. Non-significant stenoses were more frequently classified as pathological intimal thickening (46 (25%) vs 3 (7%), p<0.05), although TCFA (more vulnerable plaque) was distributed equally (pu200a=u200a0.18). Conclusion: No evident association exists between the degree of stenosis and plaque composition or vulnerability, as evaluated non-invasively by MSCT and invasively by VH IVUS.